Intrabody-mediated control of immune reactions

Abstract

The present invention is directed to methods of altering the regulation of the immune system, e.g., by selectively targeting individual or classes of immunomodulatory receptor molecules (IRMs) on cells comprising transducing the cells with an intracellularly expressed antibody, or intrabody, against the IRMs. In a preferred embodiment the intrabody comprises a single chain antibody against an IRM, e.g, MHC-1 molecules.

1 . A method of inhibiting an undesired MHC class 1 immune associated reaction comprising transducing a cell that can be involved in the undesired MHC class 1 immune associated reaction with a first gene encoding an antibody, wherein said antibody when expressed will bind in the cell to a target molecule involved in the undesired MHC class 1 immune associated reaction, expressing the antibody and letting said antibody bind to said target molecule, and also transducing said cell with a second gene encoding an MHC-1 analog that is deficient in its ability to initiate an MHC class 1 reaction, wherein said MHC-1 analog will not initiate the NK (Natural Killer) reaction.  
     
     
         2 . The method of  claim 1 , wherein the antibody comprises a single chain antibody.  
     
     
         3 . The method of  claim 1 , wherein said antibody binds to an MHC Class I component selected from the group consisting of MHC Class Iα chains, β2 microglobulin, calnexin, transporter associated with antigen processing (TAP) and tapasin.  
     
     
         4 . The method of  claim 1 , wherein the target molecule is an MHC class I molecule, and the undesired immune reaction is tissue rejection during transplantation.  
     
     
         5 . The method of  claim 4 , wherein the cell is an antigen presenting cell.  
     
     
         6 . The method of  claim 1 , wherein the gene encoding the antibody is in an RNA or DNA vector.  
     
     
         7 . The method of  claim 6 , wherein the gene encoding the antibody is in a DNA vector.  
     
     
         8 . The method of  claim 1 , wherein the MHC-1 analog is an MHC-1 molecule that lacks its cytoplasmic domain.